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EClinicalMedicine Jun 2024Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause...
BACKGROUND
Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults.
METHODS
This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206.
FINDINGS
Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%-68.2%), compared with 63.4% in the control group (95% CI 61.8%-65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%-20.7%), compared with 18.8% in the control group (95% CI 17.4%-20.2%) a difference of +0.6 percentage points (95% CI -1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination.
INTERPRETATION
In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease.
FUNDING
Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.
PubMed: 38774675
DOI: 10.1016/j.eclinm.2024.102616 -
Acta Microbiologica Et Immunologica... May 2024The worldwide burden of disease of bacterial meningitis remains high, despite the decreasing incidence following introduction of routine vaccination campaigns.The aim of...
The worldwide burden of disease of bacterial meningitis remains high, despite the decreasing incidence following introduction of routine vaccination campaigns.The aim of our study was to evaluate the epidemiological and bacteriological profile of paediatric bacterial meningitis (BM) in Tunisian children, during the period 2003-2019, following the implementation of Haemophilus influenzae type b (Hib) vaccine (April 2011) and before 10-valent pneumoccocal conjugate vaccine (PCV10) introduction to the childhood immunization program.All bacteriologically confirmed cases of BM admitted to children's hospital of Tunis were recorded (January 2003 to April 2019). Serogroups of Neisseria meningitidis (Nm) and serotypes of Streptococcus pneumoniae (Sp) and H. influenzae (Hi) and antibiotic resistance were determined using conventional and molecular methods.Among 388 cases, the most frequent species were Sp (51.3%), followed by Nm (27.5%) and Hi (16.8%). We observed a significant decrease in Hi BM rate during the conjugated Hib vaccine use period (P < 0.0001). The main pneumococcal serotypes were 14, 19F, 6B, 23F and 19A and the serotype coverage of PCV10, PCV13, PCV15 and PCV20 was 71.3 and 78.8%, 79.4 and 81.9% respectively. The most frequent Nm serogroup was B (83.1%). Most Hi strains were of serotype b (86.9%). High levels of resistance were found: Sp and Nm to penicillin (respectively 60.1 and 80%) and Hi to ampicillin (42.6%). All meningococcal and Hi isolates were susceptible to third-generation cephalosporins and 7.2% of pneumococcal strains had decreased susceptibility to these antibiotics.The Hib conjugate vaccine decreased the rate of BM. Sp dominated the aetiology of BM in children in Tunisia. Conjugate vaccines introducing decreases not only BM cases but also antimicrobial resistance.
PubMed: 38771654
DOI: 10.1556/030.2024.02208 -
Journal of the American Chemical Society Jun 2024Inspired by the specificity of α-(2,9)-sialyl epitopes in bacterial capsular polysaccharides (CPS), a doubly fluorinated disaccharide has been validated as a vaccine...
Inspired by the specificity of α-(2,9)-sialyl epitopes in bacterial capsular polysaccharides (CPS), a doubly fluorinated disaccharide has been validated as a vaccine lead against serogroups C and/or B. Emulating the importance of fluorine in drug discovery, this molecular editing approach serves a multitude of purposes, which range from controlling α-selective chemical sialylation to mitigating competing elimination. Conjugation of the disialoside with two carrier proteins (CRM197 and PorA) enabled a semisynthetic vaccine to be generated; this was then investigated in six groups of six mice. The individual levels of antibodies formed were compared and classified as highly glycan-specific and protective. All glycoconjugates induced a stable and long-term IgG response and binding to the native CPS epitope was achieved. The generated antibodies were protective against MenC and/or MenB; this was validated by SBA and OPKA assays. By merging the fluorinated glycan epitope of MenC with an outer cell membrane protein of MenB, a bivalent vaccine against both serogroups was created. It is envisaged that validation of this synthetic, fluorinated disialoside bioisostere as a potent antigen will open new therapeutic avenues.
Topics: Animals; Mice; Halogenation; N-Acetylneuraminic Acid; Meningococcal Vaccines; Neisseria meningitidis, Serogroup B; Meningitis, Meningococcal
PubMed: 38768956
DOI: 10.1021/jacs.4c03179 -
MSphere Jun 2024serogroup B (NmB) strains have diverse antigens, necessitating methods for predicting meningococcal serogroup B (MenB) vaccine strain coverage. The genetic...
serogroup B (NmB) strains have diverse antigens, necessitating methods for predicting meningococcal serogroup B (MenB) vaccine strain coverage. The genetic Meningococcal Antigen Typing System (gMATS), a correlate of MATS estimates, predicts strain coverage by the 4-component MenB (4CMenB) vaccine in cultivable and non-cultivable NmB isolates. In Taiwan, 134 invasive, disease-causing NmB isolates were collected in 2003-2020 (23.1%, 4.5%, 5.2%, 29.8%, and 37.3% from individuals aged ≤11 months, 12-23 months, 2-4 years, 5-29 years, and ≥30 years, respectively). NmB isolates were characterized by whole-genome sequencing and vaccine antigen genotyping, and 4CMenB strain coverage was predicted using gMATS. Analysis of phylogenetic relationships with 502 global NmB genomes showed that most isolates belonged to three global hyperinvasive clonal complexes: ST-4821 (27.6%), ST-32 (23.9%), and ST-41/44 (14.9%). Predicted strain coverage by gMATS was 62.7%, with 27.6% isolates covered, 2.2% not covered, and 66.4% unpredictable by gMATS. Age group coverage point estimates ranged from 42.9% (2-4 years) to 66.1% (≤11 months). Antigen coverage estimates and percentages predicted as covered/not covered were highly variable, with higher estimates for isolates with one or more gMATS-positive antigens than for isolates positive for one 4CMenB antigen. In conclusion, this first study on NmB strain coverage by 4CMenB in Taiwan shows 62.7% coverage by gMATS, with predictable coverage for 29.8% of isolates. These could be underestimated since the gMATS calculation does not consider synergistic mechanisms associated with simultaneous antibody binding to multiple targets elicited by multicomponent vaccines or the contributions of minor outer membrane vesicle vaccine components.IMPORTANCEMeningococcal diseases, caused by the bacterium (meningococcus), include meningitis and septicemia. Although rare, invasive meningococcal disease is often severe and can be fatal. Nearly all cases are caused by six meningococcal serogroups (types), including meningococcal serogroup B. Vaccines are available against meningococcal serogroup B, but the antigens targeted by these vaccines have highly variable genetic features and expression levels, so the effectiveness of vaccination may vary depending on the strains circulating in particular countries. It is therefore important to test meningococcal serogroup B strains isolated from specific populations to estimate the percentage of bacterial strains that a vaccine can protect against (vaccine strain coverage). Meningococcal isolates were collected in Taiwan between 2003 and 2020, of which 134 were identified as serogroup B. We did further investigations on these isolates, including using a method (called gMATS) to predict vaccine strain coverage by the 4-component meningococcal serogroup B vaccine (4CMenB).
Topics: Humans; Taiwan; Meningococcal Vaccines; Neisseria meningitidis, Serogroup B; Infant; Child, Preschool; Child; Adult; Adolescent; Young Adult; Whole Genome Sequencing; Meningococcal Infections; Phylogeny; Antigens, Bacterial; Male; Female; Genotype; Vaccination Coverage
PubMed: 38752729
DOI: 10.1128/msphere.00220-24 -
Human Vaccines & Immunotherapeutics Dec 2024COVID-19, caused by SARS-CoV-2, and meningococcal disease, caused by , are relevant infectious diseases, preventable through vaccination. Outer membrane vesicles (OMVs),...
COVID-19, caused by SARS-CoV-2, and meningococcal disease, caused by , are relevant infectious diseases, preventable through vaccination. Outer membrane vesicles (OMVs), released from Gram-negative bacteria, such as , present adjuvant characteristics and may confer protection against meningococcal disease. Here, we evaluated in mice the humoral and cellular immune response to different doses of receptor binding domain (RBD) of SARS-CoV-2 adjuvanted by C:2a:P1.5 OMVs and aluminum hydroxide, as a combined preparation for these pathogens. The immunization induced IgG antibodies of high avidity for RBD and OMVs, besides IgG that recognized the Omicron BA.2 variant of SARS-CoV-2 with intermediary avidity. Cellular immunity showed IFN-γ and IL-4 secretion in response to RBD and OMV stimuli, demonstrating immunologic memory and a mixed Th1/Th2 response. Offspring presented transferred IgG of similar levels and avidity as their mothers. Humoral immunity did not point to the superiority of any RBD dose, but the group immunized with a lower antigenic dose (0.5 μg) had the better cellular response. Overall, OMVs enhanced RBD immunogenicity and conferred an immune response directed to too.
Topics: Animals; Mice; Immunoglobulin G; Neisseria meningitidis; Female; Antibodies, Viral; COVID-19; SARS-CoV-2; Adjuvants, Immunologic; COVID-19 Vaccines; Immunity, Cellular; Immunity, Humoral; Mice, Inbred BALB C; Meningococcal Infections; Spike Glycoprotein, Coronavirus; Adjuvants, Vaccine; Aluminum Hydroxide; Immunization; Antibody Affinity; Antibodies, Bacterial; Meningococcal Vaccines; Immunologic Memory; Th1 Cells
PubMed: 38745461
DOI: 10.1080/21645515.2024.2346963 -
JAMA Jun 2024
Topics: Humans; Infant; Meningitis, Meningococcal; Meningococcal Vaccines; United States; Child, Preschool; Child; Adolescent; Young Adult; Adult; Nigeria
PubMed: 38728043
DOI: 10.1001/jama.2024.7727 -
Vaccine May 2024The rates of nasopharyngeal meningococcal carriage in healthcare workers are unknown. Meningococcal vaccine is recommended for risk groups but healthcare workers are not...
The rates of nasopharyngeal meningococcal carriage in healthcare workers are unknown. Meningococcal vaccine is recommended for risk groups but healthcare workers are not included in risk groups for many countries. Herein, we aimed to investigate the nasopharyngeal meningococcal carriage rates, basal and after one dose of Men-ACWY-DT vaccine response on the 30th day by evaluating meningococcus IgG antibody levels and decolonization at month six after vaccination among the detected carriers. Nasopharyngeal swab samples were taken before vaccination to evaluate meningococcal carriage in healthcare workers. All participants received a single dose of Men-ACWY-DT vaccine. Serum samples were collected immediately before vaccination and again on day 30 post-vaccination. Antibodies in the stored sera were analyzed using the ELISA method. Participants who were determined to carry meningococci at the initial visit underwent another round of nasopharyngeal swab tests six months post-vaccination to check for decolonization. Between November 2020 and May 2021, we evaluated samples from 100 physicians [52 % females, 28.28 ± 4.45 (min: 24, max: 49)]. The majority of the physicians worked in the emergency department (45 %), followed by the infectious diseases clinic (14 %). Fifty-eight physicians had a history of at least one contact with a meningococcus-infected patient, and 53 (91.4 %) had used prophylactic antibiotics at least once due to this exposure. None of the study group nasopharyngeal swab cultures were positive for Neisseria meningitidis. Before the Men-ACWY-DT vaccine, anti-meningococcus IgG positivity was detected in the serum samples of only 3 (3 %) participants. By day 30 after vaccination, 48 % of participants showed positive for antibodies. As we didn't detect nasopharyngeal carriage in any participants, we didn't evaluate decolonization among carriers six months post-vaccination. Notably, detection of antibodies was evident in about half of the participants on day 30 after receiving a single dose of the Men-ACWY-DT vaccine.
PubMed: 38719693
DOI: 10.1016/j.vaccine.2024.05.004 -
BMJ Open May 2024The effectiveness of antibiotics for treating gonococcal infections is compromised due to escalating antibiotic resistance; and the development of an effective... (Observational Study)
Observational Study
Comprehensive observational study evaluating the enduring effectiveness of 4CMenB, the meningococcal B vaccine against gonococcal infections in the Northern Territory and South Australia, Australia: study protocol.
INTRODUCTION
The effectiveness of antibiotics for treating gonococcal infections is compromised due to escalating antibiotic resistance; and the development of an effective gonococcal vaccine has been challenging. Emerging evidence suggests that the licensed meningococcal B (MenB) vaccine, 4CMenB is effective against gonococcal infections due to cross-reacting antibodies and 95% genetic homology between the two bacteria, and that cause the diseases. This project aims to undertake epidemiological and genomic surveillance to evaluate the long-term protection of the 4CMenB vaccine against gonococcal infections in the Northern Territory (NT) and South Australia (SA), and to determine the potential benefit of a booster vaccine doses to provide longer-term protection against gonococcal infections.
METHODS AND ANALYSES
This observational study will provide long-term evaluation results of the effectiveness of the 4CMenB vaccine against gonococcal infections at 4-7 years post 4CMenB programme implementation. Routine notifiable disease notifications will be the basis for assessing the impact of the vaccine on gonococcal infections. Pathology laboratories will provide data on the number and percentage of positive tests relative to all tests administered and will coordinate molecular sequencing for isolates. Genome sequencing results will be provided by SA Pathology and Territory Pathology/New South Wales Health Pathology, and linked with notification data by SA Health and NT Health. There are limitations in observational studies including the potential for confounding. Confounders will be analysed separately for each outcome/comparison.
ETHICS AND DISSEMINATION
The protocol and all study documents have been reviewed and approved by the SA Department for Health and Well-being Human Research Ethics Committee (HREC/2022/HRE00308), and the evaluation will commence in the NT on receipt of approval from the NT Health and Menzies School of Health Research Human Research Ethics Committee. Results will be published in peer-reviewed journals and presented at scientific meetings and public forums.
Topics: Humans; Gonorrhea; Northern Territory; Meningococcal Vaccines; Neisseria gonorrhoeae; South Australia; Observational Studies as Topic; Female
PubMed: 38719318
DOI: 10.1136/bmjopen-2023-079144 -
The Journal of Infection Jul 2024The last COVID-19 vaccine offered to all adults in England became available from November 2021. The most recent booster programme commenced in September 2023. Bivalent...
Effectiveness of autumn 2023 COVID-19 vaccination and residual protection of prior doses against hospitalisation in England, estimated using a test-negative case-control study.
INTRODUCTION
The last COVID-19 vaccine offered to all adults in England became available from November 2021. The most recent booster programme commenced in September 2023. Bivalent BA.4-5 or monovalent XBB.1.5 boosters were given. During the study period, the JN.1 variant became dominant in England.
METHODS
Vaccine effectiveness against hospitalisation was estimated throughout using the test-negative case-control study design where positive PCR tests from hospitalised individuals are cases and comparable negative PCR tests are controls. Multivariable logistic regression was used to assess vaccine effectiveness against hospitalisation with the test result as the outcome, vaccination status as the primary exposure variable of interest and confounder adjustment.
RESULTS
There was no evidence of residual protection for boosters given as part of previous campaigns. There were 28,916 eligible tests included to estimate the effectiveness of the autumn 2023 boosters in those aged 65 years and older. VE peaked at 50.6% (95% CI: 44.2-56.3%) after 2-4 weeks, followed by waning to 13.6% (95% CI: -11.7 to 33.2%). Estimates were generally higher for the XBB.1.5 booster than the BA.4-5 booster, but this difference was not statistically significant. Point estimates were highest against XBB sub-lineages. Effectiveness was lower against both JN.1 and EG.5.1 variants with confidence intervals non-overlapping with the effectiveness of the XBB sub-lineages at 2-4 weeks for EG.5.1 where VE was 44.5% (95% CI: 20.2-61.4%) and at 5-9 weeks for JN.1 where VE was 26.4% (95%CI: -3.4 to 47.6%).
CONCLUSIONS
The recent monovalent XBB.1.5 and bivalent BA.4-5 boosters provided comparable and good protection against hospitalisation, however there was evidence of lower VE against hospitalisation of these boosters against JN.1.
Topics: Humans; COVID-19; England; Hospitalization; Case-Control Studies; Aged; Male; SARS-CoV-2; Female; COVID-19 Vaccines; Vaccine Efficacy; Immunization, Secondary; Vaccination; Aged, 80 and over; Middle Aged; Adult
PubMed: 38719110
DOI: 10.1016/j.jinf.2024.106177 -
The Pediatric Infectious Disease Journal May 2024The effect of the Bacille Calmette-Guérin (BCG) vaccine on the immunogenicity of separately administered serogroup C meningococcal vaccine and other vaccinations was...
The effect of the Bacille Calmette-Guérin (BCG) vaccine on the immunogenicity of separately administered serogroup C meningococcal vaccine and other vaccinations was examined in 28 infants randomized to receive BCG at age ≤7 days, at 3 months or after study completion. Immunogenicity of the serogroup C meningococcal vaccine and other routine vaccines might be improved when BCG is administered in early infancy.
PubMed: 38717982
DOI: 10.1097/INF.0000000000004373